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Extrapolation of Efficacy from Adults to Pediatric Patients of Drugs for Treatment of Partial Onset Seizures: A Regulatory Perspective

Journal Article · · Clinical Pharmacology and Therapeutics
DOI:https://doi.org/10.1002/cpt.2681· OSTI ID:2425677
 [1];  [2];  [3];  [2];  [2];  [2];  [2];  [4];  [4];  [4];  [3];  [3];  [5]
  1. Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland USA; Takeda Cambridge Massachusetts USA
  2. Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland USA
  3. Office of Neuroscience, Office of New Drugs, Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland USA
  4. Division of Neurology 2, Office of New Drugs, Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland USA
  5. Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland USA; Haichang Biotech/The WhiteOak Group Rockville Maryland USA
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The US Food and Drug Administration (FDA) has concluded that the efficacy of drugs approved for the treatment of partial onset seizures (POS) in adults can be extrapolated to pediatric patients 1 month of age and above and that independent efficacy trials in this pediatric population are no longer needed. This paper focuses on the dosing, pharmacokinetic (PK), exposure‐response, and clinical information that were leveraged from the approved drugs for the treatment of POS to conduct analyses that supported extrapolation of efficacy in pediatric patients. Clinical data from trials for eight drugs (levetiracetam, oxcarbazepine, topiramate, lamotrigine, gabapentin, perampanel, tiagabine, and vigabatrin) approved in both adults and pediatric patients for the treatment of POS were analyzed. Comparisons of exposures at approved doses, placebo response, and model‐based exposure‐response relationships were performed. Based on disease similarity, similar response to intervention, and similar exposure‐response relationships in adults and pediatric patients, it was concluded that extrapolation of efficacy in pediatric patients aged 1 month and above is acceptable. PK analysis to determine pediatric dose and regimens that provide drug exposure similar to that known to be effective in adult patients with POS will be required, along with long‐term open‐label safety data in pediatric patients.

Research Organization:
Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
DOE Contract Number:
SC0014664
OSTI ID:
2425677
Journal Information:
Clinical Pharmacology and Therapeutics, Journal Name: Clinical Pharmacology and Therapeutics Journal Issue: 4 Vol. 112; ISSN 0009-9236
Publisher:
American Society for Clinical Pharmacology & Therapeutics - Wiley
Country of Publication:
United States
Language:
English

References (8)

Clinical Development of Antiepileptic Drugs for Children journal January 2007
Pregabalin Population Pharmacokinetic and Exposure‐Response Analyses for Focal Onset Seizures in Children (4–16 years) and Adults, to Support Dose Recommendations in Children journal January 2021
Role of Quantitative Clinical Pharmacology in Pediatric Approval and Labeling journal April 2016
Efficacy of antiepileptic drugs in adults predicts efficacy in children journal October 2012
Antiepileptic Drug Development in Children journal January 2008
Extrapolating evidence of antiepileptic drug efficacy in adults to children ≥2 years of age with focal seizures: The case for disease similarity journal July 2017
Clinical Drug Development in Epilepsy Revisited: A Proposal for a New Paradigm Streamlined Using Extrapolation journal September 2016
Extrapolation of Adult Data and Other Data in Pediatric Drug-Development Programs journal October 2011

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